Autologous fat transplants influence compensatory white adipose tissue mass increases after lipectomy

Direct tests of the hypothesized total body fat regulatory system have been accomplished by partial surgical lipectomy. This usually results in the restoration of the lipid deficit through compensatory increases in nonexcised white adipose tissue (WAT) masses of ground squirrels, laboratory rats, and mice, as well as Siberian and Syrian hamsters. We challenged this hypothesized total body fat regulatory system by testing the response of Siberian hamsters to 1) lipid deficits [lipectomy; primarily bilateral epididymal WAT (EWAT) removal], 2) lipid surfeits (addition of donor EWAT with no lipectomy), 3) no net change in lipid [EWAT or inguinal WAT (IWAT) lipectomy with the excised fat replaced to a new location (autologous)], 4) lipectomy with the same pad (EWAT lipectomy only) added from a sibling (nonautologous), and 5) sham surgeries for each treatment. Food intake generally was not affected. Body mass was not affected across all treatments. Grafts approximately 3 mo later had normal appearance both macro- and microscopically and were revascularized. The normal lipectomy-induced compensatory increases in nonexcised WAT masses surprisingly were exaggerated with autologous EWAT transplants, but not for autologous IWAT or nonautologous EWAT transplants. There was no compensatory decrease in native WAT masses with nonautologous EWAT additions. Collectively, only lipectomy triggered reparation of the lipid deficit, but the other manipulations did not, suggesting a system biased toward rectifying decreases in lipid or an inability of the hypothesized total body fat regulatory system to recognize WAT transplants.     

White adipose tissue sensory nerve denervation mimics lipectomy-induced compensatory increases in adiposity

The sensory innervation of white adipose tissue (WAT) is indicated by the labeling of sensory bipolar neurons in the dorsal root ganglion after retrograde dye placement into WAT. In addition, immunoreactivity (ir) for sensory-associated neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P in WAT pads also supports the notion of WAT sensory innervation. The function of this sensory innervation is unknown but could involve conveying the degree of adiposity to the brain. In tests of total body fat regulation, partial surgical lipectomy triggers compensatory increases in the mass of nonexcised WAT, ultimately resulting in restoration of total body fat levels in Siberian hamsters and other animals. The signal that triggers this compensation is unknown but could involve disruption of WAT sensory innervation that accompanies lipectomy. Therefore, a local and selective sensory denervation was accomplished by microinjecting the sensory nerve neurotoxin capsaicin bilaterally into epididymal WAT (EWAT) of Siberian hamsters, whereas controls received vehicle injections. Additional hamsters had bilateral EWAT lipectomy (EWATx) or sham lipectomy. As seen previously, EWATx resulted in significantly increased retroperitoneal WAT (RWAT) and inguinal WAT (IWAT) masses. Capsaicin treatment significantly decreased CGRP- but not tyrosine hydroxylase-ir, attesting to the diminished and selective sensory innervation. Capsaicin-treated hamsters also had increased RWAT and, to a lesser degree, IWAT mass largely mimicking the WAT mass increases seen after lipectomy. Collectively, these data suggest the possibility that information related to peripheral lipid stores may be conveyed to the brain via the sensory innervation of WAT.     

A Role for Testosterone in the Maintenance of Seasonally Appropriate Body Mass but not in Lipectomy-Induced Body Fat Compensation in Siberian Hamsters

The purpose of this study was to test whether serum testosterone (T) concentrations characteristic of reproductively active, long-day-housed Siberian hamsters are necessary for compensatory increases in nonexcised fat pads following removal of epididy-mal white adipose tissue (EWAT) and/or for the maintenance of seasonally appropriate body weights in these hamsters. Long-day-housed hamsters were castrated or left intact, sham or EWAT lipectomized, and given T or cholesterol (C) implants. All groups had ad libitum food access except for two castrated T-treated groups that were pair-fed to their C-treat-ed counterparts to control for effects of T on food intake. C-treated castrates had decreased body weights compared with all other groups, suggesting a role of T in the maintenance of seasonally appropriate body mass. Since the T-treated hamsters pair-fed to these T-deficient animals exhibited seasonally appropriate body weights and fat pad masses, T does not appear to affect these parameters through the modulation of food intake. All fat pads of C-treated animals were smaller than those of ad libitum- or pair-fed, T-treated castrates; however, EWAT was the only fat pad that was smaller in the C-treated sham-lipectomized group than in gonad-intact sham-lipectomized hamsters. This result may indicate an enhanced sensitivity of EWAT to T. The effects of T on fat pad mass were not associated with proportionate changes in lipoprotein lipase activity, suggesting that the major effect of T on fat accumulation occurs through other mechanisms in this species. C-treated lipectomized hamsters compensated for the body fat deficit 8 weeks after lipectomy via statistically nonsignificant increases in retroperitoneal and inguinal WAT mass. This finding suggests that, whereas T is necessary for maintenance of seasonally-appropriate body weight, it is not necessary for fat pad compensation after EWAT lipectomy.     

Sensory or sympathetic white adipose tissue denervation differentially affects depot growth and cellularity

Functional and histological evidence for the sympathetic nervous system (SNS) innervation of white adipose tissue (WAT) exists for several species; however, its sensory innervation has only been shown in laboratory rats, and its function is unclear. We tested the effects of sensory and SNS innervation of Siberian hamster epididymal and inguinal WAT (EWAT and IWAT) by assessing calcitonin gene-related peptide (CGRP)- and tyrosine hydroxylase-immunoreactivity (ir), respectively. Next, we tested the role of the sensory innervation of WAT on growth and cellularity because WAT surgical denervation increases pad mass via selective increases in fat cell number, an effect ascribed to SNS denervation but that could be due to the accompanying surgical disruption of WAT sensory innervation. Sensory denervation was accomplished via multiple local microinjections of capsaicin into WAT, and its effects were compared with those of surgical denervation. Surgically denervated IWAT and EWAT showed significantly decreased tyrosine hydroxylase-ir and CGRP-ir, whereas capsaicin-treated WAT had only significantly decreased CGRP-ir. Surgically denervated pad masses were significantly increased; this was accompanied by increased total fat cell number in IWAT, with no change in fat cell size. EWAT only showed a significant increase in the number of small- to medium-sized adipocytes (75-125 mum diameter). By contrast, sensory-denervated pad masses were unchanged, but IWAT showed significantly increased average fat cell size. Collectively, these data provide immunohistochemical evidence for sensory and SNS innervation of WAT in Siberian hamsters and differential control of WAT cellularity by these innervations, as well as the ability of locally applied capsaicin to selectively reduce WAT sensory innervation.     

Short photoperiod exposure increases adipocyte sensitivity to noradrenergic stimulation in Siberian hamsters

Siberian hamsters (Phodopus sungorus) exhibit a naturally occurring, reversible seasonal obesity with body fat peaking in long "summerlike" days (LDs) and reaching a nadir in short "winterlike" days (SDs). These SD-induced decreases in adiposity are mediated largely via sympathetic nervous system (SNS) innervation of white adipose tissue (WAT), as indicated by increased WAT norepinephrine (NE) turnover. We examined whether SDs also increase sensitivity to NE-stimulated lipolysis. This was accomplished by measuring NE- and beta3-adrenoceptor (beta3-AR) agonist (BRL-37344)-induced lipolysis (glycerol release) as well as NE-induced cAMP accumulation by inguinal, epididymal, and retroperitoneal WAT (IWAT, EWAT, and RWAT) in isolated adipocytes of LD- and SD-housed hamsters. SDs increased potency/efficacy of NE-triggered lipolysis in a temporally and fat pad-specific manner. Thus when WAT pad mass decreased most rapidly (5 wk of SDs), potency (sensitivity/EC50) and efficacy (maximal response asymptote) of NE-stimulated lipolysis were increased for all WAT pads and also at 10 wk for IWAT compared with their LD counterparts. SD enhancement of lipolysis was similar for NE and BRL-37344 in IWAT adipocytes. These results, coupled with our previous demonstration that SDs upregulate WAT beta3-AR mRNA expression, suggest that increased beta3-ARs mediated the SD-induced increased NE sensitivity. NE-stimulated adipocyte accumulation of cAMP was greater after 5 wk of SDs for IWAT and EWAT and after 10 wk of SDs for IWAT compared with LDs, with no photoperiod effect for RWAT. Therefore, the SD-induced increase in SNS drive to WAT and increased sensitivity to this drive may work together to increase lipolysis in SDs.     

Direct innervation of white fat and adrenal medullary catecholamines mediate photoperiodic changes in body fat

Seasonal adjustments in Siberian hamster adiposity are triggered by day length changes [i.e., short "winter-like" days (SDs) elicit body fat decreases vs. long "summer-like" days (LDs)]. These and other white adipose tissue (WAT) mass decreases traditionally have been ascribed to lipolysis triggered by sympathetically mediated, adrenal medullary released epinephrine; however, recent evidence suggests that direct sympathetic innervation of WAT also is important. Therefore, the contributions of WAT sympathetic innervation and adrenal medullary catecholamines to SD-induced decreases in adiposity were tested. Siberian hamsters were surgically bilaterally adrenal demedullated (ADMEDx) or sham ADMEDx, and all had one inguinal WAT (IWAT) pad sympathectomized via locally injected guanethidine, with the contralateral pad serving as a within-animal innervated control. One-half of the hamsters remained in LDs; the remainder was transferred to SDs. Guanethidine and ADMEDx abolished IWAT norepinephrine and adrenal epinephrine contents, respectively. Although sympathetic denervation or ADMEDx alone did not block SD-induced decreases in IWAT mass, their combination did. These results suggest that both adrenal catecholamines and the sympathetic innervation of WAT interact to decrease SD-induced decreased adiposity.     

Fat pad-specific effects of lipectomy on foraging, food hoarding, and food intake

Unlike most species, after food deprivation, Siberian hamsters increase foraging and food hoarding, two appetitive ingestive behaviors, but not food intake, a consummatory ingestive behavior. We previously demonstrated (Wood AD, Bartness TJ, Am J Physiol Regul Integr Comp Physiol 272: R783-R792, 1997) that increases in food hoarding are triggered by directly decreasing body fat levels through partial surgical lipectomy; however, we did not test if lipectomy affected foraging, nor if the magnitude of the lipid deficit affected food hoard size. Therefore, we tested whether varying the size of the lipectomy-induced lipid deficit and/or foraging effort affected foraging, food hoarding, or food intake. This was accomplished by housing adult male Siberian hamsters in a foraging/hoarding system and removing (x) both epididymal white adipose tissue (EWATx) pads, both inguinal white adipose tissue (IWATx) pads, or both EWAT and IWAT pads (EWATx + IWATx) and measuring foraging, food hoarding, and food intake for 12 wk. The lipectomy-induced lipid deficit triggered different patterns of white adipose tissue mass compensation that varied with foraging effort. Foraging for food (10 wheel revolutions to earn a food pellet) abolished the EWATx-induced compensation in IWAT pad mass. The magnitude of the lipid deficit did not engender a proportional change in any of the appetitive or consummatory ingestive behaviors. EWATx caused the greatest increase in food hoarding compared with IWATx or EWATx + IWATx, when animals were required to forage for their food. Collectively, it appears that the magnitude of a lipid deficit does not affect appetitive or consummatory behaviors; rather, when energy (foraging) demands are increased, loss of specific (gonadal) fat pads can preferentially stimulate increases in food hoarding.     

Compensation for partial lipectomy in mice with genetic alterations of leptin and its receptor subtypes

One hypothesis for the regulation of total body fat suggests that leptin is a lipostatic feedback signal that acts at brain sites involved in regulation of energy balance. The importance of leptin in recovery from partial surgical lipectomy was tested by performing bilateral epididymal lipectomy or sham surgery on wild-type and leptin-deficient ob/ob mice. Eight weeks later, nonexcised pads of lipectomized mice were increased but total carcass fat was lower than in sham-operated ob/ob mice. In experiment 2, ob/ob mice, wild-type mice, and two db/db mutants, C57BL/6J db(Lepr)/db(Lepr) (BL/6J) mice possessing short-form and circulating leptin receptors and C57BL/6J db(3J)/db(3J) (BL/3J) mice expressing only circulating receptors, were lipectomized or sham operated. Sixteen weeks later, body mass and carcass lipid were not different between sham and lipectomized ob/ob mice, wild-type mice, or BL/6J db/db mice, whereas there was incomplete (decreased carcass fat) but suggestive recovery (increased retroperitoneal fat mass and cell number) in lipectomized BL/3J db/db mice. These data indicate that leptin is not required for the regulation of total body fat.     

Subcutaneous lipectomy causes a metabolic syndrome in hamsters

The insulin resistance syndrome X is related to excess intra-abdominal adipose tissue. With lipectomy of >50% of subcutaneous adipose tissue (SQAT) in nonhibernating, adult female Syrian hamsters on high-fat (HF; 50 calorie%) diet and measurements of oral glucose tolerance, oral [(14)C]oleic acid disposal, serum triglycerides, serum leptin, liver fat, perirenal (PR) adipose tissue cellularity, and body composition, we studied the role of SQAT. Sham-operated (S) animals on HF or low-fat (LF; 12.5 calorie%) diets served as controls. After 3 mo there was no visible regrowth of SQAT but HF diet led to similar levels of body weight and body fat in lipectomized and sham-operated animals. Lipectomized (L) animals had more intra-abdominal fat as a percentage of total body fat, higher insulinemic index, a strong trend toward increased liver fat content, and markedly elevated serum triglycerides compared with S-HF and S-LF. Liver and PR adipose tissue uptake of fatty acid were similar in L-HF and S-HF but reduced vs. S-LF, and were inversely correlated with liver fat content and insulin sums during the oral glucose tolerance test. In summary, lipectomy of SQAT led to compensatory fat accumulation implying regulation of total body fat mass. In conjunction with HF diet these lipectomized hamsters developed a metabolic syndrome with significant hypertriglyceridemia, relative increase in intra-abdominal fat, and insulin resistance. We propose that SQAT, via disposal and storage of excess ingested energy, acts as a metabolic sink and protects against the metabolic syndrome of obesity.     

Effects of foraging effort on body fat and food hoarding in Siberian hamsters

Food hoard size varies inversely with body fat levels in Siberian hamsters. If food hoarding only increases when body fat decreases, then hamsters foraging for their food should only increase food hoarding when foraging efforts decrease body fat ("lipostatic hypothesis"); however, if food hoarding increases whenever there is an energy flux away from fat storage, then it should increase regardless of significant body fat decreases ("metabolic hypothesis"). Female Siberian hamsters (Phodopus sungorus) earned food pellets after completion of a programmed number of wheel revolutions (Immobilized Wheel [free access to food], Free Wheel [wheel active, free food], and 10, 50, 100, and 200 revolutions/pellet). Hamsters were killed after 19 days and inguinal, retroperitoneal, and parametrial white adipose tissue (WAT) pads (IWAT, RWAT, and PWAT, respectively) were harvested and carcass composition determined. Food hoard size increased fourfold with the availability of running wheels alone (Free Wheel), increased threefold with low foraging levels (10 and 50 revolutions/pellet), but was nearly abolished at the highest foraging level (200 revolutions/pellet). Surplus food (earned, not eaten or hoarded) was significantly greatest at the lowest level of foraging. As foraging effort increased, PWAT mass decreased the most (<10 revolutions/pellet), while RWAT and IWAT mass only were decreased at the highest foraging effort. Carcass lipid content only was significantly decreased at the highest foraging effort, yet food hoarding was nearly abolished at that level. Collectively, these results demonstrate that body fat levels and food hoarding can be uncoupled with increases in foraging effort. J. Exp. Zool. 289:162-171, 2001.     

The effect of fat removal on glucose tolerance is depot specific in male and female mice

Energy is stored predominately as lipid in white adipose tissue (WAT) in distinct anatomical locations, with each site exerting different effects on key biological processes, including glucose homeostasis. To determine the relative contributions of subcutaneous and visceral WAT on glucose homeostasis, comparable amounts of adipose tissue from abdominal subcutaneous inguinal WAT (IWAT), intra-abdominal retroperitoneal WAT (RWAT), male gonadal epididymal WAT (EWAT), or female gonadal parametrial WAT (PWAT) were removed. Gonadal fat removal in both male and female chow-fed lean mice resulted in lowered glucose levels across glucose tolerance tests. Female lean C57BL/6J mice as well as male and female lean FVBN mice significantly improved glucose tolerance, indicated by decreased areas under glucose clearance curves. For the C57BL/6J mice maintained on a high-fat butter-based diet, glucose homeostasis was improved only in female mice with PWAT removal. Removal of IWAT or RWAT did not affect glucose tolerance in either dietary condition. We conclude that WAT contribution to glucose homeostasis is depot specific, with male gonadal EWAT contributing to glucose homeostasis in the lean state, whereas female gonadal PWAT contributes to glucose homeostasis in both lean and obese mice. These data illustrate both critical differences among various WAT depots and how they influence glucose homeostasis and highlight important differences between males and females in glucose regulation.     

Compensatory growth of adipose tissue after partial lipectomy: involvement of serum factors

The regulation of body weight/fat was studied by investigating mechanisms for compensatory adipose tissue growth after removal of bilateral epididymal fat pads from male adult Wistar rats. Food intake during the first 4 weeks and energy expenditure on Days 8-10 postsurgery were not different between lipectomized and sham operated rats. During Days 29-31 post surgery, a small (2.4%) but significant (P < 0.05) increase in heat production per metabolic body size was detected in lipectomized as compared with sham operated rats. The carcass composition of lipectomized and sham operated rats was not significantly different 16 weeks after surgery. The compensatory growth was fat pad-specific: mesenteric, retroperitoneal, and inguinal fat pads, but not perirenal fat pads, were heavier in lipectomized rats than in sham operated rats as early as 4 weeks postsurgery. Examination of fat cell size distribution in the compensating pads indicated a shift toward larger cells in retroperitoneal fat, but not in inguinal fat of lipectomized as compared with sham operated rats. Serum from lipectomized rats, but not media conditioned by exposure to retroperitoneal fat pads from lipectomized rats, stimulated proliferation of preadipocytes in vitro more than that from sham operated rats. Thus, compensatory adipose tissue growth after lipectomy may be mediated, in part, by blood-borne factors that are derived from tissues other than adipose tissue.     

Reductions in total body fat decrease humoral immunity

Mounting an immune response requires substantial energy, and it is well known that marked reductions in energy availability (e.g. starvation) can suppress immune function, thus increasing disease susceptibility and compromising survival. We tested the hypothesis that moderate reductions in energy availability impair humoral immunity. Specifically, we examined the effects of partial lipectomy (LIPx) on humoral immunity in two seasonally breeding rodent species, prairie voles (Microtus ochrogaster) and Siberian hamsters (Phodopus sungorus). Animals received bilateral surgical removal of epididymal white adipose tissue (EWATx), inguinal white adipose tissue (IWATx) or sham surgeries and were injected with the antigen keyhole limpet haemocyanin (KLH) either four or 12 weeks after surgery. In prairie voles, serum anti-KLH immunoglobulin G (IgG) did not differ significantly at four weeks. At 12 weeks, serum IgG was significantly reduced in IWATx, but not EWATx animals, compared with sham-operated animals. In Siberian hamsters, both IWATx and EWATx animals reduced serum IgG at four weeks. At 12 weeks, EWATx hamsters displayed a significant compensatory increase in IWAT pad mass compared with sham-operated hamsters, and serum IgG no longer differed from sham-operated animals. There was no significant increase in EWAT in IWATx hamsters compared with sham animals and IgG remained significantly reduced in IWATx hamsters. These results suggest that reductions in energy availability can impair humoral immunity.     

Adipose tissue regeneration in 6-month-old and adult rabbits following lipectomy

The effects of surgical ablation of adipose tissue were studied in male New Zealand rabbits. They were lipectomized or sham-operated either at 6 or 12 months, ages at which size and number of adipocytes are, respectively, stabilized in this species. The lipectomized animals were subjected to removal of about 80% of the perirenal and omental and to the totality of the dorsoscapular and inguinal fat tissues. Approximately 35 and 48% of the total body fat were, thus, surgically removed, respectively, in 6- and 12-month-old rabbits. All rabbits were killed 3 months after surgery and were carefully dissected. There was no significant difference in food consumption and body weight gain between lipectomized and sham-operated rabbits. Surgical removal of dorsoscapular, inguinal, and omental fat did not lead to regeneration whereas regeneration of the perirenal fat was substantial. At sacrifice the perirenal weight reached approximately 55% of the initial weight. Regeneration of perirenal adipose tissue in adults proceeded at roughly the same rate as after lipectomy in younger rabbits. These results suggest that adipose tissue regeneration in the rabbit is site dependent.     

Kinship alters the effects of forced cohabitation on body weight,mate choice and fitness in the rat-like hamster Tscheskia triton

It has been documented that social isolation imparts deleterious effects on gregarious rodents species,but caging in group imparts such effects on solitary rodents. This study was attempted at examining how kinship to affect body weight,behavioral interaction,mate choice and fitness when we caged male and female rat-like hamsters Tscheskia triton in pair,a solitary species. We found that females paired with nonsibling males became heavier than the females paired with sibling males,but both agonistic and amicable behavior between paired males and females did not differ between sibling and nonsibling groups. This indicated that kinship might reduce females' obesity in response to forced cohabitation,and dissociation might exist between physiological and behavioral responses. Furthermore,binary choice tests revealed that social familiarity between either siblings or nonsiblings decreased their investigating time spent in opposite sex conspecific of cage mates and/or their scents as compared with those of nonmates,suggesting effects of social association on mate and kin selection of the hamsters. On the other side,both females and males caged in pair with siblings show a preference between unfamiliar siblings or their scents and the counterparts of nonsiblings after two month separation,indicating that the kin recognition of the hamsters might also rely on phenotype matching. In addition,cohabitation (or permanent presence of fathers) elicited a lower survival of pups in nonsibling pairs than sibling pairs,but did not affect litter size,suggesting that kinship affects fitness when housing male and female ratlike hamsters together. Therefore,inbreeding might be adapted for rare and endangered animals.     

Sympathetic but not sensory denervation stimulates white adipocyte proliferation

White adipocyte proliferation is a hallmark of obesity, but it largely remains a mechanistic mystery. We and others previously demonstrated that surgical denervation of white adipose tissue (WAT) triggers increases in fat cell number, but it is unknown whether this was due to preadipocyte proliferation or maturation of existing preadipocytes that allowed them to be counted. In addition, surgical denervation severs not only sympathetic but also sensory innervation of WAT. Therefore, we tested whether sympathetic WAT denervation triggers adipocyte proliferation using 5-bromo-2'-deoxyuridine (BrdU) as a marker of proliferation and quantified BrdU-immunoreactive (ir) cells that were co-labeled with AD-3-ir, an adipocyte-specific membrane protein marker. The unilateral denervation model was used for all experiments where Siberian hamster inguinal WAT (IWAT) was unilaterally denervated, the contralateral pad was sham denervated serving as a within-animal control, and then BrdU was injected systemically for 6 days. When IWAT was surgically denervated, severing both sympathetic and sensory nerves, tyrosine hydroxylase (TH)-ir, a sympathetic nerve marker, and calcitonin gene-related peptide (CGRP)-ir, a sensory nerve marker, were significantly decreased, and BrdU+AD-3-ir adipocytes were increased approximately 300%. When IWAT was selectively sensory denervated via local microinjections of capsaicin, a sensory nerve-specific toxin, CGRP-ir, but not TH-ir, was decreased, and BrdU+AD-3-ir adipocytes were unchanged. When IWAT was selectively sympathetically denervated via local microinjections of 6-hydroxy-dopamine, a catecholaminergic-specific toxin, TH-ir, but not CGRP-ir, was significantly decreased, and BrdU+AD-3-ir adipocytes were increased approximately 400%. Collectively, these data provide the first direct evidence that sympathetic nerves inhibit white adipocyte proliferation in vivo.     

Hypothalamic Paraventricular Nucleus Lesion Involvement in the Sympathetic Control of Lipid Mobilization

The sympathetic nervous system (SNS) innervation of white adipose tissue (WAT) is the principal initiator of lipolysis. Using pseudorabies virus, a transneuronal viral tract tracer, brain sites involved in the SNS outflow to WAT have been identified previously by us. One of these sites, the hypothalamic paraventricular nucleus (PVH) that shows predominantly unilateral sympathetic outflow from each half of the nucleus to ipsilaterally located WAT depots, was tested for laterality in lipid accumulation/mobilization in Siberian hamsters. First we tested whether unilateral PVH electrolytic lesions (PVHx) would increase lipid accumulation in WAT pads ipsilateral to the side of the PVHx. PVHx significantly increased body and WAT pad masses compared with sham PVHx; however, there was no laterality effect. In addition, bilateral PVHx increased body and WAT pad masses, as well as food intake, to a greater extent than did unilateral PVHx. We next tested for possible laterality effects on WAT lipid mobilization using food deprivation as the lipolytic stimulus in hamsters bearing unilateral or bilateral PVHx. Lipid mobilization was not prevented, as indicated indirectly by WAT mass and thus laterality of lipid mobilization could not be tested. We then tested whether removal of adrenal catecholamines via adrenal demedullation (ADMEDx) alone, or combined with bilateral PVHx, would block food deprivation–induced lipid mobilization, but neither did so. These results suggest that an intact PVH is not necessary for food deprivation–induced lipid mobilization and support the primacy of the SNS innervation of WAT, rather than adrenal medullary catecholamines, for lipid mobilization from WAT.     

Seasonal changes in adiposity: the roles of the photoperiod,melatonin and other hormones,and sympathetic nervous system

It appears advantageous for many non-human animals to store energy body fat extensively and efficiently because their food supply is more labile and less abundant than in their human counterparts. The level of adiposity in many of these species often shows predictable increases and decreases with changes in the season. These cyclic changes in seasonal adiposity in some species are triggered by changes in the photoperiod that are faithfully transduced into a biochemical signal through the nightly secretion of melatonin (MEL) via the pineal gland. Here, we focus primarily on the findings from the most commonly studied species showing seasonal changes in adiposity-Siberian and Syrian hamsters. The data to date are not compelling for a direct effect of MEL on white adipose tissue (WAT) and brown adipose tissue (BAT) despite some recent data to the contrary. Thus far, none of the possible hormonal intermediaries for the effects of MEL on seasonal adiposity appear likely as a mechanism by which MEL affects the photoperiodic control of body fat levels indirectly. We also provide evidence pointing toward the sympathetic nervous system as a likely mediator of the effects of MEL on short day-induced body fat decreases in Siberian hamsters through increases in sympathetic drive on WAT and BAT. We speculate that decreases in the SNS drive to these tissues may underlie the photoperiod-induced seasonal increases in body fat of species such as Syrian hamsters. Clearly, we need to deepen our understanding of seasonal adiposity, although, to our knowledge, this is the only form of environmentally induced changes in body fat where the key elements of its external trigger have been identified and can be traced to and through their transduction into a physiological stimulus that ultimately affects identified responses of white adipocyte physiology and cellularity. Finally, the comparative physiological approach to the study of seasonal adiposity seems likely to continue to yield significant insights into the mechanisms underlying this phenomenon and for understanding obesity and its reversal in general.     

Food deprivation-induced changes in body fat mobilization after neonatal monosodium glutamate treatment

The reversal of obesity is a difficult feat at best and is a growing problem as the obesity epidemic increases worldwide. Considerable focus has been made on the arcuate nucleus (Arc) in the control of body and lipid mass and food intake. To test the role of the Arc in body fat mobilization, we compared the effects of food deprivation on white adipose tissue (WAT) mass in adult Siberian hamsters by making exocytotic lesions of the Arc via neonatal subcutaneous injections of monosodium glutamate (MSG). MSG-treated hamsters had significantly increased body mass, total and individual WAT pad masses, and serum leptin concentrations compared with their vehicle-injected counterparts. MSG produced marked reductions in Arc Nissl staining, tyrosine hydroxylase-immunoreactive (ir) neurons, and neuropeptide Y (NPY)- and agouti-related protein (AgRP)-ir fibers compared with controls. MSG significantly decreased hypothalamic paraventricular nucleus (PVN) NPY- and AgRP fiber-ir compared with controls, likely because of Arc projections to this nucleus. MSG treatment also reduced area postrema (AP) tyrosine hydroxylase (TH)-ir fibers compared with controls. MSG treatment did not, however, block food deprivation-induced decreases in WAT pad mass compared with controls. Thus, despite considerable damage to the Arc and some of its projections to the PVN, as well as the AP, body fat was mobilized apparently normally, bringing into question the necessity of these structures for food deprivation-induced lipid mobilization. These data support recent evidence that chronically decerebrate rats, in which the forebrain is surgically isolated from the caudal brainstem, show normal food deprivation responses, including lipid mobilization.